In vivo imaging of activity-dependent synaptogenic events between dynamic axonal and dendritic filopodia within the developing brain- Connections to the development of schizophrenia and highly common …

Mounting evidence suggests that many common neurological and psychiatric disorders, such as schizophrenia, autism, and epilepsy, originate from abnormal brain circuit formation and neuron (nerve cell) growth during early development. An increasing number of studies show that in addition to genes, conditions in our surroundings can influence neuron development during early life and in later years. One important contributor to abnormal neuron growth may be altered levels of glutamate (the primary neurotransmitter that nerve cells use to send signals across synapses) and its neurotransmitting capabilities – called glutamatergic synaptic transmission. For example, a reduced glutamatergic transmission has been associated with schizophrenia and an increased level with neonatal seizures. Derek Dunfield is investigating how neurons connect with each other and how activity influences those connections during development. Specifically he is measuring the influence of glutamatergic transmission on dynamic brain circuit growth. Derek is examining real-time imaging of neurons during development using a relatively new imaging technique called two-photon microscopy and a labeling technique called single-cell electroporation. This allows him to label single neurons with different colours and watch how they interact together as they grow. Derek hopes this research will lead to better treatment and diagnosis for disabling brain disorders.

The role of the Rap GTPases and Pyk2 Protein Tyrosine Kinase in cell migration

Chemokines are small proteins that direct the migration of immune cells into and within the body’s immune system. These include B cells that become activated and mediate an immune response to infectious agents (antigens) that cause disease. Dr. Michael Gold’s laboratory is interested in understanding the function of the protein Rap1, a GTPase that is activated by binding to the nucleotide GTP. Dr. Gold’s lab has shown that Rap activation is involved in B cell migration towards certain chemokines. More recently, their research has indicated that Rap regulates the activation of Pyk2, a protein known to be required for B cell migration. As a trainee in Dr. Gold’s lab, Caylib Durand is studying how chemokine-induced signaling causes B lymphocytes and other immune cells to migrate, and how chemokine-mediated signaling activates Rap1 and Pyk2. His goal is to identify key signaling pathways that coordinate the events required for cell migration. Ultimately, Caylib’s work may indicate that Rap and Pyk2 might be good targets for drugs to regulate inflammation and immune responses.

Bioengineering for the production of cells with islet function to treat Diabetes

A significant breakthrough in diabetes research occurred in 2000, when an Edmonton research group developed a protocol for transplanting insulin-producing cells from human donors into patients with type 1 (insulin-dependent) diabetes. More than 100 successful islet transplantations have been performed worldwide, bringing realistic hope for a cure to diabetes. Since two donors on average are required to acquire sufficient islets to treat one patient, a shortage of donor islets remains a significant obstacle for widespread use of transplantation. There is a great demand for alternative sources of these cells, such as cells derived from adult stem cells produced in the laboratory. Ideally, cells would be taken from a patient. From these, the appropriate stem cells would be isolated then cultivated to produce a supply of islet cells for transplantation back into the patient. Before this can be achieved, however, researchers must optimize techniques for increasing the numbers of pancreatic islet cells that can be produced in this fashion. Corinne Hoesli’s research focuses on duct cells, which are believed to be the precursors of insulin-producing islet cells. She is working both to determine the best ways to grow these cells in-vitro and how to translate these protocols to support larger scale production. As process optimization and scale-up are typical engineering issues, she hopes that applying engineering approaches to this field of health research will help overcome the bottleneck of tissue shortage for islet transplantations.

Antiarrhythmic drug effects on sodium channel slow-type inactivation – investigation of interactions at the selectivity filter

The selective passage of ions through channels in cellular membranes provides the molecular basis for many cellular processes. This includes control of the initial phase of depolarizations that lead to contraction of the heart. Upon initiation of contraction, sodium ion channels open briefly, and then are inactivated by a portion of the protein that “”plugs”” the channel pore, preventing further ion passage. Recently, a much slower form of channel inactivation has been discovered, which researchers believe is controlled by a separate, co-existing mechanism. One theory suggests that slow inactivation occurs when the protein components responsible for the selective passage of sodium ions constrict, causing complete occlusion of the pore during periods of prolonged or rapid openings. Certain drug classes work by blocking sodium channels, such as local anesthetics and a sub-class of anti-arrhythmic drugs, both of which can be used to treat an irregular heartbeat. There is limited understanding of how these drugs affect, or are affected by, the slow inactivation process.

GIS and tobacco research: Understanding impact of tobacco industry promotional activities on youth smoking behaviour

Smoking is the major cause of preventable death in Canada, accounting for more than 45,000 premature deaths per year and 30 per cent of all cancer deaths. Most smokers begin to smoke as teenagers, and tobacco advertising and promotion are among the main motivators for tobacco use, especially in youth. Currently, tobacco companies are spending the majority of their marketing dollars in retail stores, compared to any other advertising venue. Since most teenagers shop at convenience stores at least once a week, adolescents are routinely exposed to tobacco advertising. Little research has examined the extent and impact of these “Point of Purchase” (POP) activities in Canada. Helen Hsu is studying the links between smoking prevalence among youth and environmental influences, including POP advertising, pricing, signage and retail locations. She is using Geographic Information System technology to gather and analyze social-demographic, economic and geographic information. Her work could help explain the impact of tobacco industry activities on adolescent tobacco use across Canada, and provide insight into the effectiveness of tobacco control strategies in schools and communities. This information will be useful for setting public health policies and developing tobacco control programs.

Characterization of the Caenorhabditis elegans bZIP transcription factor C34D1.5 a possible DAF-16 target implicated in longevity

Although aging is a normal biological process, it is also associated with a host of mental and physical illnesses. Many of these illnesses have their basis in genetic function. A key area of focus for researchers examining age-related health issues is the insulin-like growth factor pathway, which plays an important role in cell growth, uptake of nutrients and aging. Genetic researchers often use a microscopic worm named C. elegans for their studies, because this organism shares many of the essential biological characteristics of human biology. Genes controlled by the insulin pathway in C. elegans, flies and mice have been shown to affect longevity, including a gene discovered by PhD trainee Victor Jensen in his honours thesis. Victor is conducting research to study how this gene activity affects longevity. He is also studying a potential connection between this gene and genes involved in stress response to environmental challenges. By learning more about this gene’s role in longevity and stress response, he hopes to contribute to therapeutic and nutritional strategies to counter the negative effects of aging.

Characterization of mesenchymal stem cell differentiation and self-renewal in the context of an in vivo model of bone regeneration

Stem cells are normally located in bone marrow, but when grown in the appropriate environment, they have the unique potential to transform into and generate several different types of cells in the body. Many medical researchers believe stem cells have the potential to revolutionize medicine, enabling doctors to repair specific tissues or to grow organs. However, the processes that control their development are not fully understood at present. Mesenchymal stem cells (MSC) are derived from adult bone marrow and have been shown to specifically differentiate into cells of connective tissues, such as ligament, tendon and bone. Due to the relatively recent identification of MSCs, there is still much debate about the basic mechanisms that underlie MSC physiology. There have been several reports to indicate that MSCs can contribute to bone healing; however whether this effect is sustained through the long-term has yet to be determined. Aaron Joe’s research focus is to further current understanding of MSCs and to explore the potential for MSC-based therapies in clinical regenerative medicine. He is investigating whether combining MSCs with a new biomaterial can create a long-lasting source of bone cells that, when transplanted into diseased bone, will result in complete and sustained healing of bone defects. Aaron hopes his research will provide insight into the contribution of transplanted MSCs to bone healing. Specifically his work may lead to the development of prototypic regenerative therapy for severe bone loss associated with replacement hip surgery.

Estimating the economic burden of treating HIV/AIDS in the era of highly active antiretroviral therapy (HAART) with simulation modeling

AIDS is a chronic, life-threatening disease caused by the human immunodeficiency virus (HIV). HIV attacks the immune system, making people more susceptible to certain types of cancers and infection. Untreated patients generally survive about 10 years. Highly active antiretroviral therapy (HAART), which became widely available in 1996, has significantly reduced illness and death from HIV infection. However, the treatment regimen is expensive and the cumulative costs of treatment are growing as life expectancy increases. A crude estimate of treatment costs for HIV patients in Canada — drugs, physician and hospital visits and lab tests — exceeds $800 million a year. Because this cost estimate is based on simplistic assumptions, health care managers have asked for more accurate tools to help make policy decisions in HIV/AIDS management. Getting a handle on actual costs is particularly important given emerging evidence of an increase in the HIV incidence rate, in BC and across Canada. Karissa Johnston is developing a more sophisticated computer simulation model to accurately estimate the annual and lifetime medical costs for treating people infected with HIV. This tool will also predict how costs will change for various treatment protocols and population groups. Health planners will be able to use these estimates to assess the costs and benefits of disease prevention, drug compliance and various treatment strategies.

Development and characterization of a new human model of Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a specific type of leukemia in which there is a latent, or dormant, phase for several years before the rapid onset of fatal symptoms. This type of leukemia is difficult to study because the CML cells usually die when they are grown in laboratory conditions. Using human embryonic stem cells for CML research may be a viable option, as this type of cell readily grows in vitro and has the ability to develop into the type of blood cell affected by CML. The cells could be used to mimic some of the genetic changes seen in leukemia to identify important changes that trigger or block the progression of this disease. Melanie Kardel is working to develop techniques for creating leukemic cells from human embryonic stem cells in the laboratory. Because these cells could be grown in the lab for longer periods of time, more extensive studies than are currently possible could be performed, leading to the identification of new targets for therapy. Once targets are identified, this system would also be used to test the potential success of the therapies before they advance to clinical trial.

The structure and function of the Striatum in First Episode Psychosis

Schizophrenia is a complex and devastating mental disorder, marked by a breakdown in the relation between thoughts, feelings, and actions. Symptoms include delusions, hallucinations, disorganized language, and disorganized or catatonic behaviour. About one percent of the population develops schizophrenia, usually in late adolescence or early adulthood. However, the cause of this disabling illness remains unclear. Recent evidence suggests disturbances in early brain development may predispose people to schizophrenia. The striatum, a region of the brain involved in motor, sensory, and cognitive processes, is thought to be involved in the development of the disorder. Babak Khorram is using magnetic resonance imaging (MRI) technology to compare brain scans of schizophrenia patients and healthy volunteers. Babak is investigating whether abnormalities of the striatum are present when the illness begins, or emerge as a result of treatment, and the effect on patients’ cognitive functioning and treatment. The results could enable clinicians to screen people thought to be susceptible to the disorder, due to genetic and environmental factors. The research could ultimately improve diagnosis and treatment of schizophrenia.